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Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 55 records · Page 3Linked to original sources

Work in dry cleaning and the incidence of cancer of the oral cavity, larynx, and oesophagus.

OBJECTIVES: To investigate whether employment in dry cleaning, and potential exposure to perchloroethylene (PCE), were associated with increased risk of carcinoma of the oral cavity and pharynx, larynx, oesophagus, and gastric cardia. METHODS: Two population based case-control studies were carried out. There were 491 cases of carcinoma of the oral cavity and pharynx, 235 of the larynx, and 404 of the oesophagus and gastric cardia. 724 controls were selected by random digit dialing. Personal interviews ascertained information on lifetime job histories, cigarette use, alcohol consumption, and other potential risk factors. The probability and level of exposure to PCE were estimated from the scientific literature. RESULTS: People who worked in dry cleaning tended to consume less alcohol and cigarettes than the general population. The adjusted odds ratio (OR) associated with ever having worked in dry cleaning was 1.6 (95% confidence interval (95% CI) = 0.6 to 4.4) for all cancer types together. The strongest associations were with laryngeal (OR 2.7; 95% CI 0.6 to 10.9) and oesophageal squamous cell carcinomas (OR 3.6; 95% CI 0.5 to 27.0). For laryngeal cancer, the relative risk increased with number of years employed in the dry cleaning industry (P = 0.14. The two cases of oesophageal squamous cell carcinomas had worked in dry cleaning for only a short time. Analyses of subsites showed higher risks for supraglottic laryngeal cancer (OR 5.7; 95% CI 1.0 to 32.1) and cancer of the tongue (OR 2.3; 95% CI 0.4 to 12.6). Analyses of exposure to PCE yielded similar results. CONCLUSIONS: These findings could easily be explained by chance; nevertheless, they are consistent with previous reports of excess risk of oesophageal, laryngeal, and tongue cancer, and suggest that previous studies of dry cleaners that could not control for alcohol and cigarette use may have underestimated the relative risks of such cancers.

Adenocarcinoma↗

Primary Hodgkin's disease of the sigmoid colon: a case report and review of the literature.

We report the case of an 81-year-old man who underwent a segmental resection of the sigmoid colon for severe diverticular disease. Histopathologic diagnosis revealed extranodal Hodgkin's disease, and the diagnosis was confirmed by immunohistochemistry. The incidence of extranodal Hodgkin's disease is rare and represents an infrequent occurrence as a gastrointestinal neoplasm and primary gastrointestinal lymphoma. A review of the literature for gastrointestinal lymphomas with emphasis on the occurrence of Hodgkin's disease, the diagnostic features, and the site of gastrointestinal tract involvement is reported.

Aged↗

Viral peptide specific induction of MHC class II expression by murine T cell clones.

We report that I-Ab-restricted T cell clones, elicited by influenza infection of C57BL/10 mice and specific for the hemagglutinin peptide HA1 186-205, express class II. They respond to peptide stimulation by IL release (IL-3 or IFN-gamma) without a requirement for APC but do not proliferate. Moreover, surface expression of class II requires de novo synthesis in the presence of the stimulatory peptide and is inhibited by coculture with TCR-specific Ab, or brefeldin A or cycloheximide. Clonotypic specificity of peptide induction was confirmed by failure of other allele specific peptides to enhance class II expression. Addition of the viral peptide to T cells induced homotypic adhesion, which provides a physical basis for stabilization of class II-peptide complexes at the cell surface. Extinction of class II expression was evident in the corresponding T cell hybridomas, which might account for the failure to report class II expression by murine T cells. Control studies indicated that class II was not passively acquired from APC by demonstrating 1) failure of processed Ag to induce class II expression, 2) allo-class II (Ak) was not acquired by coculture with peptide and semisyngeneic (H-2 b/k) APC, 3) absence of class II expression by a NP peptide-specific Th2 clone under identical culture conditions, and most significantly, 4) reverse-transcriptase PCR amplification and surface expression of class II using highly purified preparations of FACS-selected CD4+ class II- cells cocultured with the stimulatory peptide.

Alleles↗

Oral contraceptives and invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives.

Data from a hospital-based case-control study collected between 1979 and 1988 in 10 participating hospitals in eight countries were analyzed to determine whether use of combined oral contraceptives alters the risks of invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. Information on prior use of oral contraceptives, suspected risk factors for cervical cancer, and history of cytologic screening was ascertained from interviews with 271 women with adenocarcinomas, 106 with adenosquamous carcinomas, and a large pool of hospitalized controls, from which 2,887 were matched to the cases included in this report. History of smoking and anogenital warts and blood specimens for measurement of herpes simplex and cytomegalovirus antibodies were obtained from subsets of these women, as was a sexual history from a subset of their husbands. The epidemiologic features and associations with oral contraceptives were similar for adenocarcinoma and adenosquamous carcinoma. For both types combined, risk increased with duration of oral contraceptive use, was highest in recent and current users, and declined with time since cessation of use. These trends in risk were strongest for cancers that occurred in women under age 35 years, and the association with risk was somewhat stronger for high compared with low progestin potency products. The strength of the observed relation with oral contraceptives was about the same as has been observed for invasive squamous cell cervical carcinomas. Women who have used oral contraceptives should be considered at increased risk of adenomatous cervical carcinomas.

Adenocarcinoma↗

Alcoholism: independent predictor of survival in patients with head and neck cancer.

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.

Adult↗

Prostitution, condom use, and invasive squamous cell cervical cancer in Thailand.

Cervical cancer is probably caused by a sexually transmitted agent. A case-control study was conducted in three hospitals in Thailand to investigate further the role of male sexual behavior, particularly regarding sexual contacts with prostitutes, in the development of this disease. Data were obtained from interviews with 225 married women with invasive squamous cell cervical carcinoma and 791 hospitalized controls, all of whom reported having only one sexual partner, and from interviews with their husbands. Risk of cervical cancer was strongly related to the women's husbands having visited prostitutes without using a condom when the husbands were less than 30 years old. A strong increasing trend in risk in relation to decreasing frequency of the husbands' condom use with prostitutes was observed, and a weaker increasing trend in risk with husbands' estimated lifetime total number of visits to prostitutes was found. The average latent period between the women's likely initial exposure to a sexually transmitted oncogenic agent and her diagnosis of invasive cervical cancer was about a quarter of a century. Regular use of condoms by customers of prostitutes could reduce the number of invasive cervical cancer cases in the general population of Thailand by at least one fourth.

Adult↗

Multicentre international liver tumour study protocol of the case-control study on hepatocellular cancer.

Toxicological evidence has recently shown that cyproterone acetate (CPA) is associated with increased adduct formation in liver cell cultures that was interpreted as a possible sign for genotoxicity. Likewise, a few spontaneous reports of liver cancer associated to CPA were published. This led to an alert announced by the German Drug Regulators. One reason to design a case-control study on hepatocellular cancer (HCC) and oral contraceptives (OC's) use (and specific subtypes such as CPA-containing ones) was that other clinical or pharmacoepidemiological studies were not available which dealt with this suspicion. This idea got support from the fact that most of the earlier case-control studies on HCC and OC were small, did not sufficiently control for confounding by: hepatitis B and C, exposure at work, use of other potentially hepatotoxic drugs and also did not distinguish between different types of OC's. Objectives, hypotheses, methods used and subjects studied are described in this paper. The study began in six countries (Germany, United Kingdom, France, Italy, Spain, Greece) on 1 July 1994. It will be finished by the end of June 1996, and first results can be expected by the end of 1996 or early 1997.

Journal Article↗

Intrauterine devices and endometrial cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship between intrauterine device (IUD) use and the development of endometrial cancer was assessed in data from seven countries that were collected between 1979 and 1988 for a multinational hospital-based case-control study. Two hundred twenty-six cases of endometrial cancer were compared with 1,529 controls matched for age, hospital, and year of interview. No significant association between use of an IUD and risk of endometrial cancer was observed (OR = 0.74, 95% CI = 0.4-1.33). There were no trends in risk with respect to duration of use, time since first use, or ages at first or last use. No cases had used a copper IUD (OR = 0, 95% CI = 0-1.71). Although women over age 55 who had used an IUD were at significantly increased risk, this unexpected finding is based on small numbers of users and requires independent confirmation. These results, along with those from other studies, provide reassurance that risk of endometrial cancer is unlikely to be increased by use of an IUD.

Adult↗

Reduced risk of ovarian cancer in women with a tubal ligation or hysterectomy. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives.

Possible relationships between tubal ligation and hysterectomy and epithelial ovarian cancer were assessed in data that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. Histologically confirmed incident cases (n = 393) were compared with controls (n = 2563) matched on age, hospital, and year of interview. A nonsignificant reduction in risk was observed for tubal ligation [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.48-1.08] and hysterectomy (OR, 0.58; 95% CI, 0.26-1.27). There was no trend in risk with time since tubal ligation. The possible protective effect of tubal ligation was greatest in women of parity less than four. The apparent protective effect of tubal ligation was seen only for clear cell (OR, 0.32; 95% CI, 0.006-2.50) and endometrioid (OR, 0.20; 95% CI, 0.046-1.46) tumors, suggesting a hormonal mechanism for the observed associations.

Adult↗

Epidemiology of smallpox in west Pakistan. III. Outbreak detection and interlocality transmission. 1971.

During one year, 121 outbreaks of variola major were detected in 99 of the 1717 localities within a rural area of West Pakistan with a total population of approximately 1.2 million. Only 19% of the outbreaks, representing 36% of the 1040 investigated cases, were officially reported, although potential strengths in the government surveillance system were also identified. Persistence of smallpox within the area depended on introductions from the outside, and more than one-half of all outbreaks of known source could be ultimately traced to cities. Within the study area, outbreaks with the largest numbers of cases and those in the larger communities were the ones from which smallpox was most frequently transported. The frequency with which variola was introduced into localities was directly related to population size and to the presence of medical care facilities. Trips between localities by infected individuals were extremely rare events. They were made most often during the late fall and winter, primarily during the incubation period of the disease, and did not differ in purpose, means or destination from journeys unassociated with smallpox. Individuals at relatively high risk of becoming introducers included the unvaccinated (primarily children under five), the unschooled and those not native to the area. Vaccination priorities based on these findings could increase the efficiency of smallpox eradication efforts.

Disease Outbreaks↗

Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies.

BACKGROUND: Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. DESIGN: Pooled results from two case-control studies. SETTING: New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). PARTICIPANTS: A total of 1768 women with breast cancer and 13,905 controls, most of whom were younger than 55 years. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer in women who had used DMPA. RESULTS: The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). CONCLUSIONS: The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use.

Adolescent↗

Immunodominance with progenitor B cell diversity in the neutralizing antibody repertoire to influenza infection.

We report striking immunodominance in the neutralizing antibody responses of major histocompatibility complex congenic mice to natural infection with influenza virus (H3N2 subtype), as deduced by sequencing the hemagglutinin (HA) genes of monoclonal antibody (mAb)-selected mutant viruses. A majority of mAb, established from individual BALB/c (H-2d) mice, select mutant viruses containing the same single amino acid substitution in the membrane distal ecto-domain, HA1 198 A-->E, whereas changes at either HA1 158 G-->E or HA1 198 A-->E are selected for by mAb from BALB.K (H-2k) donors. The structural basis for immunodominance, and potential diversity of progenitor B cells, was investigated by sequence analysis of H and L chain gene rearrangements in mAb specific for HA1 158 or HA1 198. No correlation was found between antibody specificity and VH or VL gene usage, and a minimum of three to six progenitor cells contributed to the individual's repertoire for a single antigenic site. However, in a further analysis of the HA1 158-specific antibody response of CBA/Ca (H-2k) donors, there was highly restricted light chain gene usage. Focusing of the immune repertoire to limited regions of the HA molecule during a primary viral infection may be a significant factor in immune pressure for antigenic variation, particularly since there is no evident restriction in the antibody response to immunization.

Animals↗

Immune receptor repertoire for influenza haemagglutinin.

An extensive analysis was made of receptor specificity and gene usage in the neutralising antibody (mAb) and Class II-restricted T cell responses to influenza haemagglutinin (HA) following natural infection of MHC (H-2(k) or H-2(d)) congenic mice with X31 virus (H3N2 subtype). Despite the diversity of available antigenic sites on the HA1 subunit, there was striking immunodominance in the mAb response as deduced by sequencing the HA genes of escape mutants and the corresponding antibody H and L chain gene rearrangements. Similarly, Class II restricted T cell responses of individual donors focused on a single antigenic site, or immunodominant peptide; and PCR sequence analysis of T cell receptor (alpha beta) gene usage indicated that T cell memory was derived from a single progenitor cell. Focusing of the immune repertoire to limited regions of the HA molecule during a primary viral infection may be a significant factor in immune pressure for antigenic variation.

Amino Acid Sequence↗

Cervical carcinoma in situ and use of depot-medroxyprogesterone acetate (DMPA). WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship of depot-medroxyprogesterone acetate (D-MPA) use to risk of cervical carcinoma in situ was investigated using data from a large multi-national, hospital-based case-control study. To avoid possible detection bias from Pap smear screening, final analyses were restricted to a subset of cases with symptoms at the time of their diagnosis of cervical carcinoma in situ. Relative to nonusers, the risk was elevated in women who had ever used DMPA and increased with duration of use. Decreasing trends in relative risk with times since first and last uses were observed in long-term users. Results from another portion of this same study did not show a relationship of invasive cervical cancer to DMPA use. These findings suggested that if DMPA increases the risk of cervical carcinoma in situ then either this is a reversible effect, or the cervical lesions induced by DMPA tend not to progress to invasive disease.

Adult↗

Depot-medroxyprogesterone acetate (DMPA) and risk of invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

A hospital-based case-control study was conducted in two hospitals in Bangkok, Thailand, and in one hospital each in Chiang Mai, Thailand, Mexico City, Mexico and Nairobi, Kenya. One purpose of this study was to determine whether the long-acting progestational contraceptive, depot-medroxyprogesterone acetate (DMPA), alters risk of invasive cervical carcinomas with adenomatous histological features. Information on prior use of DMPA, screening for cervical cancer, and the suspected risk factors for this disease was ascertained from interviews of 239 women with adenocarcinomas and 85 women with adenosquamous carcinomas, as well of from a large pool of controls, 2534 of whom were matched to the cases included in this report. For selected subsets of these women, a smoking history was also elicited, blood specimens were collected for measurement of antibodies against herpes simplex and cytomegalovirus, and information on sexual behavior was obtained from interviews of their husbands. The relative risk (and 95% confidence interval) of adenomatous cervical carcinomas in women who ever used DMPA was estimated to be 0.75 (0.51, 1.11). No trends in risk were observed with duration of DMPA use, times since first or last use, or age at first use. The results provide reassurance that use of DMPA for over four years does not enhance risk of adenomatous cervical carcinomas, and risk is not increased after a potential latent period of over 12 years since initial exposure.

Adenocarcinoma↗

Combined oral contraceptives and risk of cervical carcinoma in situ. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

BACKGROUND: Although the possible influence of oral contraceptives on risk of cervical carcinoma in situ has been the subject of multiple prior investigations, the results have been inconsistent. METHODS: Data from a multinational, collaborative case-control study were analysed to investigate further this possible relationship. To assess potential screening bias, some statistical analyses were restricted to subgroups of cases with and without symptoms at the time of their diagnosis. RESULTS: Relative risk estimates in relation to various features of oral contraceptive use tended to be highest for asymptomatic disease, lowest for disease presenting with vaginal bleeding, and intermediate for disease presenting with other symptoms, suggesting the presence of a screening bias. In women with vaginal bleeding, who are least likely to have been detected by routine screening, no elevated risk of cervical carcinoma in situ was observed in relation to ever having used combined oral contraceptives, but there was an increased risk in users of over 60 months' duration. An increasing trend in risk with duration of use was most pronounced in these women who first used oral contraceptives in the past 5-10 years; and in women who used oral contraceptives for more than 60 months, risk declined with time since last use. CONCLUSION: These findings could reflect a reversible effect of long-term use of oral contraceptives at an intermediate stage in the carcinogenic process, or a non-causal relationship due to unidentified sources of bias or confounding.

Adult↗

Prolonged lactation and endometrial cancer. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

BACKGROUND: The risk of endometrial cancer is related to oestrogen levels, showing an increased risk with increasing endogenous or exogenous oestrogen stimulation and a reduced risk when oestrogen is opposed by progesterone. During breastfeeding, the reduction of endogenous oestrogen exposure is larger than that of progesterone, suggesting that breastfeeding may possibly reduce the risk of endometrial cancer. METHODS: The relationship between lactation and endometrial cancer was assessed in data from six countries, including four developing countries, that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. In all, 136 cases were compared with 933 controls matched on age, hospital, and year of interview. Standardized questionnaires, administered in the local language, ascertained information on the length of time breastfed, age started and stopped breastfeeding, reproductive and contraceptive practices, and other risk factors for endometrial cancer. Conditional logistic regression was used to control for the confounding effects of gravidity and age at menarche. RESULTS: Significant decreasing trends in risk were observed with increasing duration of lactation, and with months of breastfeeding per pregnancy. Risk was lowest in women who had most recently lactated, and the apparent protective effect declined with time since cessation of breastfeeding, so that there was no evidence for a protective effect after age 55 even in women who had breastfed for over 5 years. CONCLUSIONS: The long-term lactation that takes place in developing countries probably reduces the risk of endometrial cancer, but this effect may not persist into the ages at which this disease is most common.

Adolescent↗

Of colic and rumbling in the guts.

Infant colic is a common disorder of doubtful aetiology. The known facts have been interpreted in a historical and geographical context. The apparent increase in incidence of the condition in the Westernized world during the twentieth century may reflect the technological advances and social changes that have occurred in recent years.

Colic↗